Ovarian small cell carcinoma

Summary

Ovarian small cell carcinoma (MONDO:0003795) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 2 clinical trials. Molecularly, SMARCA4 Loss confers sensitivity to Palbociclib + Ribociclib + Abemaciclib in Ovarian Small Cell Carcinoma (CIViC Level D). Top therapeutic interventions include pembrolizumab.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Clinical trials: 2
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian small cell carcinoma
Mondo ID	MONDO:0003795
EFO	EFO:1000431
Orphanet	370396
DOID	DOID:6179
NCIT	C27390
UMLS	C2212006
MedGen	389177
GARD	0010411
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	yes

Also known as: ovarian small cell cancer · ovarian small cell carcinoma · ovarian small cell NEC · ovarian small cell neuroendocrine carcinoma · ovary small cell carcinoma · SCCO · small cell carcinoma of ovary · small cell carcinoma of the ovary · small cell ovarian carcinoma

Data availability: 6 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › neuroendocrine carcinoma › small cell carcinoma › ovarian small cell carcinoma

Related subtypes (17): extrahepatic bile duct small cell adenocarcinoma, colon small cell neuroendocrine carcinoma, urinary bladder small cell neuroendocrine carcinoma, esophageal small cell neuroendocrine carcinoma, ampulla of vater small cell neuroendocrine carcinoma, Bartholin gland small cell carcinoma, thymus small cell carcinoma, cervical small cell carcinoma, endometrial small cell carcinoma, gallbladder small cell neuroendocrine carcinoma, gastric small cell neuroendocrine carcinoma, laryngeal small cell carcinoma, pancreatic small cell neuroendocrine carcinoma, prostate small cell carcinoma, salivary gland small cell carcinoma, ureter small cell carcinoma, small cell lung carcinoma

Subtypes (2): pulmonary type ovarian small cell carcinoma, hypercalcemic type ovarian small cell carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cervix squamous epithelium	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCA4	8,138

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCA4	P51532	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the non-canonical BAF (ncBAF) complex	1	671.8×	0.012	SMARCA4
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.012	SMARCA4
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.012	SMARCA4
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.012	SMARCA4
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.012	SMARCA4
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.012	SMARCA4
Regulation of endogenous retroelements	1	368.4×	0.012	SMARCA4
Interleukin-7 signaling	1	317.2×	0.012	SMARCA4
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.012	SMARCA4
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.012	SMARCA4
MITF-M-dependent gene expression	1	181.3×	0.014	SMARCA4
RMTs methylate histone arginines	1	146.4×	0.014	SMARCA4
Transcriptional regulation by RUNX1	1	146.4×	0.014	SMARCA4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.014	SMARCA4
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.014	SMARCA4
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.014	SMARCA4
TCF dependent signaling in response to WNT	1	117.7×	0.014	SMARCA4
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	SMARCA4
MITF-M-regulated melanocyte development	1	114.2×	0.014	SMARCA4
Signaling by WNT	1	112.0×	0.014	SMARCA4
Chromatin organization	1	81.6×	0.019	SMARCA4
Chromatin modifying enzymes	1	72.3×	0.019	SMARCA4
Epigenetic regulation of gene expression	1	71.4×	0.019	SMARCA4
Signaling by Interleukins	1	64.2×	0.021	SMARCA4
Nervous system development	1	42.9×	0.030	SMARCA4
Cytokine Signaling in Immune system	1	40.8×	0.030	SMARCA4
RNA Polymerase II Transcription	1	22.5×	0.053	SMARCA4
Gene expression (Transcription)	1	17.8×	0.064	SMARCA4
Generic Transcription Pathway	1	15.1×	0.073	SMARCA4
Developmental Biology	1	14.5×	0.074	SMARCA4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of glucose mediated signaling pathway	1	5617.3×	0.005	SMARCA4
RNA polymerase I preinitiation complex assembly	1	3370.4×	0.005	SMARCA4
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.005	SMARCA4
positive regulation of signal transduction by p53 class mediator	1	1203.7×	0.005	SMARCA4
neural retina development	1	936.2×	0.005	SMARCA4
negative regulation of androgen receptor signaling pathway	1	936.2×	0.005	SMARCA4
host-mediated activation of viral transcription	1	887.0×	0.005	SMARCA4
nucleosome disassembly	1	802.5×	0.005	SMARCA4
regulation of G0 to G1 transition	1	674.1×	0.005	SMARCA4
regulation of nucleotide-excision repair	1	601.9×	0.005	SMARCA4
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.005	SMARCA4
positive regulation of T cell differentiation	1	455.5×	0.005	SMARCA4
positive regulation of Wnt signaling pathway	1	383.0×	0.005	SMARCA4
transcription initiation-coupled chromatin remodeling	1	383.0×	0.005	SMARCA4
positive regulation of myoblast differentiation	1	366.4×	0.005	SMARCA4
positive regulation of stem cell population maintenance	1	343.9×	0.005	SMARCA4
positive regulation of double-strand break repair	1	343.9×	0.005	SMARCA4
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.006	SMARCA4
positive regulation of miRNA transcription	1	290.6×	0.006	SMARCA4
negative regulation of cell differentiation	1	285.6×	0.006	SMARCA4
positive regulation of cell differentiation	1	267.5×	0.006	SMARCA4
heterochromatin formation	1	255.3×	0.006	SMARCA4
positive regulation of cold-induced thermogenesis	1	163.6×	0.009	SMARCA4
negative regulation of cell growth	1	144.0×	0.009	SMARCA4
chromatin remodeling	1	73.0×	0.018	SMARCA4
nervous system development	1	45.9×	0.027	SMARCA4
positive regulation of cell population proliferation	1	33.6×	0.035	SMARCA4
negative regulation of DNA-templated transcription	1	31.6×	0.036	SMARCA4
positive regulation of DNA-templated transcription	1	27.9×	0.039	SMARCA4
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	SMARCA4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMARCA4	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SMARCA4	230	Binding:207, ADMET:12, Functional:11

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SMARCA4	230

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

2 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SMARCA4
CAMIBIRSTAT	2	SMARCA4

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	SMARCA4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04602377	PHASE2	RECRUITING	Addition of Pembrolizumab to the Standard of Care Chemotherapy in Patient With SCCOHT
NCT01970696	Not specified	RECRUITING	International Ovarian & Testicular Stromal Tumor Registry

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMBROLIZUMAB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
SMARCA4 Loss	Palbociclib + Ribociclib + Abemaciclib	Sensitivity/Response	CIViC D	EID7154